transcortin
{{Short description|Protein found in humans}}
{{Infobox gene}}
Transcortin, also known as corticosteroid-binding globulin (CBG) or serpin A6, is a protein produced in the liver in animals. In humans it is encoded by the SERPINA6 gene. It is an alpha-globulin.{{cite journal |vauthors=Hammond GL, Smith CL, Goping IS, Underhill DA, Harley MJ, Reventos J, Musto NA, Gunsalus GL, Bardin CW | title = Primary structure of human corticosteroid binding globulin, deduced from hepatic and pulmonary cDNAs, exhibits homology with serine protease inhibitors | journal = Proc Natl Acad Sci U S A | volume = 84 | issue = 15 | pages = 5153–7 |date=August 1987 | pmid = 3299377 | pmc = 298812 | doi =10.1073/pnas.84.15.5153 | bibcode = 1987PNAS...84.5153H | doi-access = free }}{{cite journal |vauthors=Byth BC, Billingsley GD, Cox DW | title = Physical and genetic mapping of the serpin gene cluster at 14q32.1: allelic association and a unique haplotype associated with alpha 1-antitrypsin deficiency | journal = Am J Hum Genet | volume = 55 | issue = 1 | pages = 126–33 |date=July 1994 | pmid = 7912884 | pmc = 1918218 }}{{cite web | title = Entrez Gene: SERPINA6 serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 6| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=866}}
Function
This gene encodes an alpha-globulin protein with corticosteroid-binding properties. This is the major transport protein for glucocorticoids and progestins in the blood of most vertebrates. The gene localizes to a chromosomal region containing several closely related serine protease inhibitors (serpins).
Binding
Transcortin binds several steroid hormones at high rates:
- Cortisol - Approximately 90% of the cortisol in circulation is bound to transcortin. (The rest is bound to serum albumin.) Cortisol is thought to be biologically active only when it is not bound to transcortin.{{citation needed|date=March 2016}}
- Cortisone{{cite book | author1 = E. Edward Bittar | author2 = Neville Bittar | title = Molecular and Cellular Endocrinology | url = https://books.google.com/books?id=sSHhmGqyXhcC&pg=PA238 | access-date = 23 August 2012 | year = 1997 | publisher = Elsevier | isbn = 978-1-55938-815-3 | page = 238}}
- Deoxycorticosterone (DOC)
- Corticosterone - About 78% of serum corticosterone is bound to transcortin.
- Aldosterone - Approximately 17% of serum aldosterone is bound to transcortin, while another 47% is bound to serum albumin. The remaining 36% is free.{{cite book | title = Principles and Practice of Endocrinology and Metabolism | url = https://books.google.com/books?id=FVfzRvaucq8C&pg=PA712 | access-date = 23 August 2012 | date = 24 April 2001 | publisher = Lippincott Williams & Wilkins | isbn = 978-0-7817-1750-2 | page = 712}}
- Progesterone - Approximately 18% of serum progesterone is bound to transcortin, while another 80% of it is bound to serum albumin. The remaining 2% is free.{{cite book | author = Negi | title = Introduction To Endocrinology | url = https://books.google.com/books?id=7Ev2mV4c_vUC&pg=PA268 | access-date = 23 August 2012 | year = 2009 | publisher = PHI Learning Pvt. Ltd. | isbn = 978-81-203-3850-0 | page = 268}}
- 17α-Hydroxyprogesterone
In addition, approximately 4% of serum testosterone is bound to transcortin.{{cite journal | vauthors = Dunn JF, Nisula BC, Rodbard D | title = Transport of steroid hormones: binding of 21 endogenous steroids to both testosterone-binding globulin and corticosteroid-binding globulin in human plasma | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 53 | issue = 1 | pages = 58–68 | date = July 1981 | pmid = 7195404 | doi = 10.1210/jcem-53-1-58 | url = http://jcem.endojournals.org/cgi/pmidlookup?view=long&pmid=7195404 | access-date = 23 August 2012 | archive-date = 14 December 2019 | archive-url = https://web.archive.org/web/20191214212905/http://jcem.endojournals.org/cgi/pmidlookup?view=long&pmid=7195404 | url-status = dead }} A similarly small fraction of serum estradiol is bound to transcortin as well.{{Citation needed|date=August 2012}}
Synthesis
Transcortin is produced by the liver and is increased by estrogens.{{cite journal |vauthors=Musa BU, Seal US, Doe RP | title = Elevation of certain plasma proteins in man following estrogen administration: a dose-response relationship | journal = J. Clin. Endocrinol. Metab. | volume = 25 | issue = 9 | pages = 1163–6 |date=September 1965 | pmid = 4284083 | doi = 10.1210/jcem-25-9-1163 }}
Clinical significance
Mutations in this gene are rare. Only four mutations have been described, often in association with fatigue and chronic pain.{{cite journal |vauthors=Torpy DJ, Lundgren BA, Ho JT, Lewis JG, Scott HS, Mericq V | title = CBG Santiago: a novel CBG mutation | journal = J. Clin. Endocrinol. Metab. | volume = 97 | issue = 1 | pages = E151–5 |date=January 2012 | pmid = 22013108 | doi = 10.1210/jc.2011-2022 | doi-access = free }} The mechanism for these symptoms is not known. This condition must be distinguished from secondary hypocortisolism. Exogenous hydrocortisone does not appear to improve the fatigue.{{cn|date=November 2023}}
Hepatic synthesis of corticosteroid-binding globulin more than doubles in pregnancy; that is, bound plasma cortisol in term pregnancy is approximately 2 to 3 times that of nonpregnant women.{{cite book | author = Rosen MI, Shnider SM, Levinson G, Hughes | title = Shnider and Levinson's anesthesia for obstetrics | publisher = Lippincott Williams & Wilkins | location = Hagerstwon, MD | year = 2002 | page = 13 | isbn = 0-683-30665-0 }}{{cite book|author=Ann M. Gronowski|title=Handbook of Clinical Laboratory Testing During Pregnancy|url=https://books.google.com/books?id=Dt_OBgAAQBAJ&pg=PA408|date=6 May 2004|publisher=Springer Science & Business Media|isbn=978-1-59259-787-1|pages=408–}}
See also
- Serpin
- Circaseptan, 7-day biological cycle
References
{{reflist}}
Further reading
{{refbegin | 2}}
- {{cite journal |vauthors=Rosner W, Beers PC, Awan T, Khan MS |title=Identification of corticosteroid-binding globulin in human milk: measurement with a filter disk assay. |journal=J. Clin. Endocrinol. Metab. |volume=42 |issue= 6 |pages= 1064–73 |year= 1976 |pmid= 932172 |doi=10.1210/jcem-42-6-1064 }}
- {{cite journal |vauthors=Smith CL, Power SG, Hammond GL |title=A Leu----His substitution at residue 93 in human corticosteroid binding globulin results in reduced affinity for cortisol. |journal=J. Steroid Biochem. Mol. Biol. |volume=42 |issue= 7 |pages= 671–6 |year= 1992 |pmid= 1504007 |doi=10.1016/0960-0760(92)90107-T |s2cid=45601231 }}
- {{cite journal | author=Brotherton J |title=Cortisol and transcortin in human seminal plasma and amniotic fluid as estimated by modern specific assays. |journal=Andrologia |volume=22 |issue= 3 |pages= 197–204 |year= 1990 |pmid= 2240617 |doi=10.1111/j.1439-0272.1990.tb01966.x |s2cid=2577211 |doi-access=free }}
- {{cite journal |vauthors=Underhill DA, Hammond GL |title=Organization of the human corticosteroid binding globulin gene and analysis of its 5'-flanking region. |journal=Mol. Endocrinol. |volume=3 |issue= 9 |pages= 1448–54 |year= 1990 |pmid= 2608068 |doi=10.1210/mend-3-9-1448 |doi-access=free }}
- {{cite journal |vauthors=Loric S, Egloff M, Domingo M, etal |title=Immunochemical characterization of corticosteroid-binding globulin in human bronchoalveolar fluid. |journal=Clin. Chim. Acta |volume=186 |issue= 1 |pages= 19–23 |year= 1990 |pmid= 2612005 |doi=10.1016/0009-8981(89)90198-8 }}
- {{cite journal |vauthors=Heubner A, Belovsky O, Müller W, etal |title=Application of liquid-liquid partition chromatography in the simultaneous purification of sex-hormone-binding globulin and corticosteroid-binding globulin. |journal=J. Chromatogr. |volume=397 |pages= 419–34 |year= 1987 |pmid= 2821037 |doi=10.1016/S0021-9673(01)85027-5 }}
- {{cite journal |vauthors=Kato EA, Hsu BR, Kuhn RW |title=Comparative structural analyses of corticosteroid binding globulin. |journal=J. Steroid Biochem. |volume=29 |issue= 2 |pages= 213–20 |year= 1988 |pmid= 3347061 |doi=10.1016/0022-4731(88)90268-3 }}
- {{cite journal |vauthors=Bardin CW, Gunsalus GL, Musto NA, etal |title=Corticosteroid binding globulin, testosterone-estradiol binding globulin, and androgen binding protein belong to protein families distinct from steroid receptors. |journal=J. Steroid Biochem. |volume=30 |issue= 1–6 |pages= 131–9 |year= 1988 |pmid= 3386241 |doi=10.1016/0022-4731(88)90085-4 }}
- {{cite journal |vauthors=Hammond GL, Langley MS |title=Identification and measurement of sex hormone binding globulin (SHBG) and corticosteroid binding globulin (CBG) in human saliva. |journal=Acta Endocrinol. |volume=112 |issue= 4 |pages= 603–8 |year= 1986 |pmid= 3751467 |doi= 10.1530/acta.0.1120603}}
- {{cite journal |vauthors=Agrimonti F, Frairia R, Fornaro D, etal |title=Circadian and circaseptan rhythmicities in corticosteroid-binding globulin (CBG) binding activity of human milk. |journal=Chronobiologia |volume=9 |issue= 3 |pages= 281–90 |year= 1983 |pmid= 7172869 }}
- {{cite journal |vauthors=Misao R, Hori M, Ichigo S, etal |title=Levels of sex hormone-binding globulin (SHBG) and corticosteroid-binding globulin (CBG) messenger ribonucleic acid (mRNAs) in ovarian endometriosis. |journal=Reprod. Nutr. Dev. |volume=35 |issue= 2 |pages= 155–65 |year= 1995 |pmid= 7734053 |doi=10.1051/rnd:19950204 |doi-access=free }}
- {{cite journal |vauthors=Misao R, Hori M, Ichigo S, etal |title=Corticosteroid-binding globulin mRNA levels in human uterine endometrium. |journal=Steroids |volume=59 |issue= 10 |pages= 603–7 |year= 1995 |pmid= 7878688 |doi=10.1016/0039-128X(94)90055-8 |s2cid=24945362 }}
- {{cite journal |vauthors=Maruyama K, Sugano S |title=Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. |journal=Gene |volume=138 |issue= 1–2 |pages= 171–4 |year= 1994 |pmid= 8125298 |doi=10.1016/0378-1119(94)90802-8 }}
- {{cite journal |vauthors=Avvakumov GV, Hammond GL |title=Glycosylation of human corticosteroid-binding globulin. Differential processing and significance of carbohydrate chains at individual sites. |journal=Biochemistry |volume=33 |issue= 19 |pages= 5759–65 |year= 1994 |pmid= 8180202 |doi=10.1021/bi00185a012 }}
- {{cite journal |vauthors=Van Baelen H, Power SG, Hammond GL |title=Decreased cortisol-binding affinity of transcortin Leuven is associated with an amino acid substitution at residue-93. |journal=Steroids |volume=58 |issue= 6 |pages= 275–7 |year= 1993 |pmid= 8212073 |doi=10.1016/0039-128X(93)90072-U |s2cid=25160586 }}
- {{cite journal |vauthors=Misao R, Nakanishi Y, Fujimoto J, etal |title=Expression of corticosteroid-binding globulin mRNA in human uterine endometrial cancers. |journal=Steroids |volume=60 |issue= 10 |pages= 720–4 |year= 1996 |pmid= 8539782 |doi=10.1016/0039-128X(95)00106-Z |s2cid=37077783 }}
- {{cite journal |vauthors=Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, etal |title=Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library. |journal=Gene |volume=200 |issue= 1–2 |pages= 149–56 |year= 1997 |pmid= 9373149 |doi=10.1016/S0378-1119(97)00411-3 }}
{{refend}}
External links
- {{MeshName|Transcortin}}
- The MEROPS online database for peptidases and their inhibitors: [http://merops.sanger.ac.uk/cgi-bin/merops.cgi?id=I04.954 I04.954]
- {{MeshName|SERPINA6+protein,+human}}
{{Carrier proteins}}
{{Alpha globulins}}
{{Serpins}}
{{Glycoproteins}}
{{Glucocorticoidics}}
{{Mineralocorticoidics}}
{{Progestogenics}}
{{Use dmy dates|date=April 2017}}